Objective To observe the intervention effect of up-regulation of miR143 on intracranial aneurysm model rats through TLR4/NF κB signaling pathway.Methods From December 2020 to September 2021, the experiment was carried out in the Department of Neurosurgery, Dongfang Hospital Affiliated to Tongji University, and 60 SPF SD rats were randomly divided into blank group, model group, up-regulated group and down-regulated group, with 15 rats in each. Except for the blank group, the other rats established intracranial aneurysm models. After successful modeling, the model group was transfected with empty plasmid, the up-regulated group was transfected with miR143 overexpression plasmid, and the down-regulated group was transfected with miR143 silencing plasmid. The expression of miR143 gene was determined by miR143 lentivirus titration. The rate of intracranial aneurysm formation in rats was evaluated, and the serum transforming growth factor β1(TGF-β1), tumor necrosis factor-α(TNF-α), vascular endothelial growth factor(VEGF), matrix metalloproteinase-2(MMP-2), MMP-9 in each group were determined. levels and protein expression of TLR4/NF-κB signaling pathway in rat intracranial arteries.Results The expression of miR-143 in the model group was higher than that in the blank group(P<0.05), and the expression of miR-143 in the down-regulated group > the model group > up-regulated group(F/P=7.484/0.001). The serum levels of TGF-β1, TNF-α, VEGF, MMP-2, and MMP-9 in the model group were higher than those in the blank group(P<0.05). The levels of TGF-β1, TNF-α, VEGF, MMP-2, MMP-9 were down-regulated group > model group > up-regulated group(F/P=10.618/0.001, 8.087/0.001, 10.091/0.001, 13.827/0.001). The protein expressions of TLR4, NF-κB and Caspase-3 in the model group were higher than those in the blank group(P<0.05), and the protein expressions of TLR4, NF-κB and Caspase-3 were down-regulated group > model group > up-regulated group(F/P=16.171/0.001, 17.878/0.001, 12.078/0.001). Conclusion Up-regulation of miR-143 gene may act on the TLR4/NF-κB signaling pathway, regulate the expression of TLR4, NF-κB, and Caspase-3 proteins, which can effectively protect rat brain tissue and effectively inhibit the occurrence and development of rat cerebral aneurysms.